Diabetes mellitus is a chronic metabolic disorder caused by an inability of the pancreas to produce sufficient amounts of the hormone insulin, resulting in the decreased ability of the body to metabolize glucose. This failure leads to hyperglycemia, i.e. the presence of an excessive amount of glucose in the blood plasma. Persistent hyperglycemia and hypoinsulinemia have been associated with a variety of serious symptoms and life-threatening long-term complications such as dehydration, ketoacidosis, diabetic coma, cardiovascular diseases, chronic renal failure, retinal damage and nerve damages with the risk of amputation of extremities. Because restoration of endogenous insulin production is not yet possible, a permanent therapy is necessary which provides constant glycemic control in order to always maintain the level of blood glucose (BG) within normal limits. Such glycemic control is achieved by regularly supplying external insulin to the body of the patient to thereby reduce the elevated levels of blood glucose.
External biologic agents such as insulin can be administered as multiple daily injections of a mixture of rapid and intermediate-acting drugs via a hypodermic syringe. Although traditional syringes have at least partly been replaced by insulin pens, the frequent injections are nevertheless very inconvenient for the patient, particularly those who are incapable of reliably self-administering injections. For some patients, substantial improvements in diabetes therapy have been achieved by the development of drug delivery devices, such as pumps, that relieve the patient of the need for syringes or drug pens and the need to administer multiple daily injections. Drug delivery devices can be constructed as an implantable device for subcutaneous arrangement or can be constructed as an external device with an infusion set for subcutaneous infusion to the patient via the transcutaneous insertion of a catheter, cannula or a transdermal drug transport such as through a patch. An example of a handheld glucose meter/controller unit is the ONETOUCH PING from JOHNSON & JOHNSON.
Drug delivery devices generally provide insulin at a “basal rate,” i.e., provide a certain amount of insulin every few minutes in a pre-programmed, daily pattern. Some drug delivery devices also permit the user to specify a “temporary basal,” in which the normal daily cycle is altered for a selected length of time. Some drug delivery devices permit the user to manually request that a “bolus,” a specified amount of insulin, be delivered at a specified time. For example, before a meal, the user can request a bolus of additional insulin be delivered to process the glucose produced by digestion of the meal. Some drug delivery devices permit the specified amount to be delivered over a period of time rather than all at once; time-extended delivery is referred to as an “extended bolus.”
Blood or interstitial glucose monitoring can be used to achieve acceptable glycemic control. The determination of blood glucose concentration can be performed by means of an episodic measuring device, such as a hand-held electronic meter, that receives blood samples on enzyme-based test strips and calculates the blood glucose value based on an electrochemical reaction of the blood and the enzyme. Continuous glucose monitoring (CGM) using a sensor inserted into or implanted in the body can also be used. A combination of a CGM and a drug-delivery device can be used to provide closed loop control of the insulin(s) being infused into the diabetic patients. For convenience, the term “artificial pancreas,” as used herein, refers to such a closed-loop system. To allow for closed-loop control of the infused insulins, proportional-integral-derivative (“PID”) controllers and model predictive controllers (MPC) have been used. Note that the term “continuous” does not require readings be updated every moment of operation. In practice, CGM generally samples glucose on a regular time scale, e.g., once per five minutes. Closed-loop control updates can be performed, e.g., in the time intervals between glucose measurements.